Chlordane and Heptachlor Are Metabolized Enantioselectively by Rat Liver Microsomes

Chlordane, heptachlor, and their metabolites are chiral persistent organic pollutants that undergo enantiomeric enrichment in the environment. This study investigated the enantioselective metabolism of both chlordane isomers and heptachlor, major components of technical chlordane, by liver microsomes prepared from male rats treated with corn oil (CO) or inducers of CYP2B (PB; phenobarbital) and CYP3A enzymes (DX; dexamethasone), isoforms induced by chlordane treatment. The extent of the metabolism of all three parent compounds was dependent on the microsomal preparation used and followed the rank order PB > DX > CO. The mass balances ranged from 49 to 130% of the parent compound added to the microsomal incubations. Both cis- and trans-chlordane were enantioselectively metabolized to oxychlordane (EF = 0.45-0.89) and 1,2-dichlorochlordene (EF = 0.42-0.90). Heptachlor was metabolized enantioselectively, with heptachlor epoxide B (EF = 0.44-0.54) being the only metabolite. Interestingly, the direction on the enrichment for oxychlordane, 1,2-dichlorochlordene, and heptachlor epoxide differed depending on the microsomal preparation. These findings demonstrate that the direction and extent of the enantioselective metabolism of both chlordane isomers and heptachlor is P450 isoform-dependent and can be modulated by the induction of P450 enzymes.